Dispersed powders of an active pharmaceutical ingredient in a pharmaceutically acceptable particulate carrier have wide applicability in the pharmaceuticals sector. They have particular importance in the area of inhalable compositions. In order to be able to be inspired into the key target sites in the lungs of patients, inhalation drugs are typically provided in micronised form with average particle sizes of up to 10 microns. A number of devices have been developed for assisting the delivery of such medicaments into the lungs of patients. In one sort of device, a dry powdered inhaler (DPI) device, the medicament to be inhaled is dispensed into an air stream produced by the inspiratory action of the patient. A large number of such devices have been developed. The device may be a single dose device (e.g. wherein drug is dispensed from a pre-metered dosage means such as a capsule) or multidose (where the drug is stored in a reservoir and then metered prior to dispersal in the air stream or the drug is pre-metered and stored in multiple dosage packs such as blisters). In many DPI devices, the particulate drug is mixed with an excipient powder of larger average particle size and the drug particles are blended with the excipient to create a fairly homogenous mixture. The larger particle size of the excipient results in the powder mixture being flowable, and the homogeneity of the mixture enable it to be metered into accurately measurable doses. This is of particular importance when only very small quantities of the drug are required in a dose. Excipient powders of this kind, and pharmaceutical powder compositions for inhalation utilising such excipients are described, for example, in U.S. Pat. No. 3,957,965.
The flow properties of the powder can be improved by controlled agglomeration of the powder. GB 1,569,911 discloses a process for the agglomeration of a drug into soft pellets using a binder to produce a paste, which is extruded through a sieve to create agglomerates. The formation of soft pellets allows diluents, such as coarse lactose, to be omitted from the composition. U.S. Pat. No. 4,161,516 also discloses the formation of soft drug pellets used to improve flowability. U.S. Pat. No. 6,371,171 discloses the preparation of spheronised agglomerates which have sufficient strength to withstand processing and packaging but which are sufficiently soft to de-agglomerate into primary particles during delivery through a breath-actuated inhaler. Examples of ingredients disclosed in U.S. Pat. No. 6,371,171, which may be formed into spheronised agglomerates, are terbutaline, budesonide and lactose.
However, there is still a need in the art for powders having improved dispersion of the pharmaceutically active ingredient in the pharmaceutically acceptable particulate carrier and with improved activity of the active ingredient.